Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C37H41N2O6 |
| Molecular Weight | 609.7312 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 3 |
| E/Z Centers | 0 |
| Charge | 1 |
SHOW SMILES / InChI
SMILES
COC1=CC2=C3[C@@H](CC4=CC=C(O)C(OC5=C(OC)C=C6CCN(C)[C@@H](CC7=CC=C(OC3=C1O)C=C7)C6=C5)=C4)[N+](C)(C)CC2
InChI
InChIKey=JFJZZMVDLULRGK-URLMMPGGSA-O
InChI=1S/C37H40N2O6/c1-38-14-12-24-19-32(42-4)33-21-27(24)28(38)16-22-6-9-26(10-7-22)44-37-35-25(20-34(43-5)36(37)41)13-15-39(2,3)29(35)17-23-8-11-30(40)31(18-23)45-33/h6-11,18-21,28-29H,12-17H2,1-5H3,(H-,40,41)/p+1/t28-,29+/m0/s1
| Molecular Formula | C37H40N2O6 |
| Molecular Weight | 608.7233 |
| Charge | 0 |
| Count |
|
| Stereochemistry | EPIMERIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 3 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Tubocurarine, a naturally occurring alkaloid, is used to treat smoking withdrawl syndrom. Tubocurarine, the chief alkaloid in tobacco products, binds stereo-selectively to nicotinic-cholinergic receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain. Two types of central nervous system effects are believed to be the basis of Tubocurarine's positively reinforcing properties. A stimulating effect is exerted mainly in the cortex via the locus ceruleus and a reward effect is exerted in the limbic system. At low doses the stimulant effects predominate while at high doses the reward effects predominate. Intermittent intravenous administration of Tubocurarine activates neurohormonal pathways, releasing acetylcholine, norepinephrine, dopamine, serotonin, vasopressin, beta-endorphin, growth hormone, and ACTH. Tubocurarine competes with acetylcholine for post-synaptic nicotinic NM receptors and blocks them.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9463808
Curator's Comment: Tubocurarine does not penetrate the normal intact blood-brain barrier.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL1907594 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15203153 |
2.0 µM [IC50] | ||
Target ID: CHEMBL1907589 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23757208 |
9.2 µM [IC50] | ||
Target ID: Q15822 Gene ID: 1135.0 Gene Symbol: CHRNA2 Target Organism: Homo sapiens (Human) |
|||
Target ID: CHEMBL2362997 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18633030 |
24.0 nM [IC50] | ||
Target ID: CHEMBL1899 |
84.1 nM [Ki] | ||
| 27.0 µM [IC50] | |||
Target ID: CHEMBL4469 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10696100 |
17.0 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Diagnostic | TUBOCURARINE CHLORIDE Approved UseTubocurarine is indicated as a diagnostic aid for myasthenia gravis when the results of tests with neostigmine or edrophonium are inconclusive Launch Date1945 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.173 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7114542/ |
16 μg/kg/min other, intravenous dose: 16 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered: |
TUBOCURARINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
117 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7114542/ |
16 μg/kg/min other, intravenous dose: 16 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered: |
TUBOCURARINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
89 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7114542/ |
16 μg/kg/min other, intravenous dose: 16 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered: |
TUBOCURARINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| likely [IC50 >100 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| no [IC50 >10 uM] | ||||
| yes [IC50 133 uM] | ||||
| yes [IC50 133 uM] | ||||
| yes [IC50 133 uM] | ||||
| yes [IC50 55.5 uM] | ||||
| yes [IC50 62.4 uM] | ||||
| yes [IC50 9.4 uM] | ||||
| yes [IC50 9.6 uM] | ||||
| yes [Inhibition 10 uM] | ||||
| yes [Inhibition 10 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes | ||||
| yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Monitoring neuronal calcium signalling using a new method for ratiometric confocal calcium imaging. | 2003-09 |
|
| GABAergic systems modulate nicotinic receptor-mediated seizures in mice. | 2003-09 |
|
| Curariform antagonists bind in different orientations to the nicotinic receptor ligand binding domain. | 2003-08-22 |
|
| Blockade of neuronal facilitatory nicotinic receptors containing alpha 3 beta 2 subunits contribute to tetanic fade in the rat isolated diaphragm. | 2003-08 |
|
| 4-Aminopyridine inhibits the neuromuscular effects of nitric oxide and 8-Br-cGMP. | 2003-07 |
|
| Neuromuscular transmission of pectoral fin muscles of the goldfish Carassius auratus. | 2003-07 |
|
| Curariform antagonists bind in different orientations to acetylcholine-binding protein. | 2003-06-20 |
|
| Dopaminergic excitation of the goat carotid body is mediated by the serotonin type 3 receptor subtype. | 2003-06-12 |
|
| Pharmacological characterization of recombinant bovine alpha3beta4 neuronal nicotinic receptors stably expressed in HEK 293 cells. | 2003-06-12 |
|
| Screening procedure for eight quaternary nitrogen muscle relaxants in blood by high-performance liquid chromatography-electrospray ionization mass spectrometry. | 2003-06-05 |
|
| Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus). | 2003-06 |
|
| Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. | 2003-05-02 |
|
| Differential modulation of light-evoked on- and off-EPSCs by paired-pulse stimulation in salamander retinal ganglion cells. | 2003-03-28 |
|
| Task-dependent presynaptic inhibition. | 2003-03-01 |
|
| Chronic intraperitoneal endotoxin treatment in rats induces resistance to d-tubocurarine, but does not produce up-regulation of acetylcholine receptors. | 2003-03 |
|
| Bisindole alkaloids from Strychnos guianensis are effective antagonists of nicotinic acetylcholine receptors in cultured human TE671 cells. | 2003-03 |
|
| D-tubocurarine reduces GABA responses in rat substantia nigra dopamine neurons. | 2003-03 |
|
| A comparison of tubocurarine, rocuronium, and cisatracurium in the prevention and reduction of succinylcholine-induced muscle fasciculations. | 2003-02 |
|
| A novel class of ligand-gated ion channel is activated by Zn2+. | 2003-01-10 |
|
| Nicotinic activation of reticulospinal cells involved in the control of swimming in lampreys. | 2003-01 |
|
| Comparative fading responses induced by mivacurium, cisatracurium, and d-tubocurarine in the evoked muscular compound action potentials of the cat. | 2003 |
|
| Characterization of an apamin-sensitive potassium current in suprachiasmatic nucleus neurons. | 2003 |
|
| Synthesis and biological evaluation of 16 beta-pyrrolidinosteroidal derivatives. | 2003 |
|
| Impairment of synaptic vesicle exocytosis and recycling during neuromuscular weakness produced in mice by 2,4-dithiobiuret. | 2002-12 |
|
| Mechanism of nicotine-evoked release of 3H-noradrenaline in human cerebral cortex slices. | 2002-12 |
|
| Orientation of d-tubocurarine in the muscle nicotinic acetylcholine receptor-binding site. | 2002-11-01 |
|
| Synthesis and neuromuscular blocking activity of 16beta-N-methylpiperazino steroidal derivatives. | 2002-11 |
|
| Nicotinic receptors regulate the release of glycine onto lamina X neurones of the rat spinal cord. | 2002-11 |
|
| Sex difference in urethral response to electrical stimulation of efferent nerves in the pudendal sensory branch of rats. | 2002-10 |
|
| Pharmacology of nicotinic receptors in preBötzinger complex that mediate modulation of respiratory pattern. | 2002-10 |
|
| Nicotinic alpha 7 receptor clusters on hippocampal GABAergic neurons: regulation by synaptic activity and neurotrophins. | 2002-09-15 |
|
| Effects of nicotine exposure on T cell development in fetal thymus organ culture: arrest of T cell maturation. | 2002-09-15 |
|
| Interaction of d-tubocurarine analogs with mutant 5-HT(3) receptors. | 2002-09 |
|
| Neuromuscular action of Bothrops lanceolatus (Fer de lance) venom and a caseinolytic fraction. | 2002-09 |
|
| Electrophysiological analysis of synaptic transmission in central neurons of Drosophila larvae. | 2002-08 |
|
| Characterization of the interactions between volatile anesthetics and neuromuscular blockers at the muscle nicotinic acetylcholine receptor. | 2002-08 |
|
| Expression of soluble ligand- and antibody-binding extracellular domain of human muscle acetylcholine receptor alpha subunit in yeast Pichia pastoris. Role of glycosylation in alpha-bungarotoxin binding. | 2002-07-26 |
|
| Modulation by nicotine of the ionic currents in guinea pig ventricular cardiomyocytes. Relatively higher sensitivity to IKr and IKl. | 2002-07 |
|
| New evidence for a presynaptic action of prednisolone at neuromuscular junctions. | 2002-07 |
|
| Characterization of [(125) I]epibatidine binding and nicotinic agonist-mediated (86) Rb(+) efflux in interpeduncular nucleus and inferior colliculus of beta2 null mutant mice. | 2002-06 |
|
| Properties of nicotinic receptors underlying Renshaw cell excitation by alpha-motor neurons in neonatal rat spinal cord. | 2002-06 |
|
| Acetylcholine increases intracellular Ca2+ in taste cells via activation of muscarinic receptors. | 2002-06 |
|
| Nicotine increases hepatic oxygen uptake in the isolated perfused rat liver by inhibiting glycolysis. | 2002-06 |
|
| Effect of glycine on synaptic transmission at the third order giant synapse of the squids Alloteuthis subulata and Loligo vulgaris. | 2002-05-31 |
|
| Fm1-43 reveals membrane recycling in adult inner hair cells of the mammalian cochlea. | 2002-05-15 |
|
| Adenosine depresses a Ca(2+)-independent step in transmitter exocytosis at frog motor nerve terminals. | 2002-04 |
|
| Evaluation of the cholinomimetic actions of trimethylsulfonium, a compound present in the midgut gland of the sea hare Aplysia brasiliana (Gastropoda, Opisthobranchia). | 2002-04 |
|
| The nature of the acetylcholine and 5-hydroxytryptamine receptors in buccal smooth muscle of the pest slug Deroceras reticulatum. | 2002-04 |
|
| Peripheral site ligands accelerate inhibition of acetylcholinesterase by neutral organophosphates. | 2001-12 |
|
| Ketamine-pancuronium-narcotic technic for cardiovascular surgery in infants--a comparative study. | 1975-11-01 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/mmx/tubocurarine-chloride.html
Diagnostic aid (myasthenia gravis)
Intravenous, 4 to 33 mcg (0.004 to 0.033 mg) per kg of body weight.
Note: It is recommended that the test be terminated within two to three minutes by intravenous injection of 1.5 mg of neostigmine, since the marked exaggeration of myasthenia gravis symptoms may result in prolonged respiratory paralysis.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12429579
D-tubocurarine (30 uM), but not alpha-bungarotoxin (alpha-BTX, 0.1 uM), attenuated the nicotine (NIC) (100 uM)-evoked release of 3H-NA.
| Substance Class |
Chemical
Created
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Edited
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| Record UNII |
W9YXS298BM
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M03AA02
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QM03AA02
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SUB15635MIG
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Tubocurarine
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DTXSID0048393
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ACTIVE MOIETY |